Direct Action of Non-Digestible Oligosaccharides against a Leaky Gut

Abstract

The epithelial monolayer is the primary determinant of mucosal barrier function, and tight junction (TJ) complexes seal the paracellular space between the adjacent epithelial cells and represent the main “gate-keepers” of the paracellular route. Impaired TJ functionality results in increased permeation of the “pro-inflammatory” luminal contents to the circulation that induces local and systemic inflammatory and immune responses, ultimately triggering and/or perpetuating (chronic) systemic inflammatory disorders. Increased gut leakiness is associated with intestinal and systemic disease states such as inflammatory bowel disease and neurodegenerative diseases such as Parkinson’s disease. Modulation of TJ dynamics is an appealing strategy aiming at inflammatory conditions associated with compromised intestinal epithelial function. Recently there has been a growing interest in nutraceuticals, particularly in non-digestible oligosaccharides (NDOs). NDOs confer innumerable health benefits via microbiome-shaping and gut microbiota-related immune responses, including enhancement of epithelial barrier integrity. Emerging evidence supports that NDOs also exert health-beneficial effects on microbiota independently via direct interactions with intestinal epithelial and immune cells. Among these valuable features, NDOs promote barrier function by directly regulating TJs via AMPK-, PKC-, MAPK-, and TLR-associated pathways. This review provides a comprehensive overview of the epithelial barrier-protective effects of different NDOs with a special focus on their microbiota-independent modulation of TJs.

Specific Human Milk Oligosaccharides Differentially Promote Th1 and Regulatory Responses in a CpG-Activated Epithelial/Immune Cell Coculture

“…The relative high abundance of fucosylated and sialylated oligosaccharides in human milk especially is unique among mammals [37]. HMOS promote the intestinal barrier integrity and support innate and adaptive immune responses [30,[38][39][40]. Aside from on the immune system via the microbiome, HMOS have also been found to directly interact with immune cells [41].…”

Effects of β-mannanase supplementation on intestinal health and growth of nursery pigs

“…In addition, the direct interaction of mannan oligosaccharides with intestinal epithelium can stimulate enterocyte proliferation. According to Mavrogeni et al. (2022) , nondigestible oligosaccharides, including mannan oligosaccharides, could directly interact with intestinal epithelial and immune cells via the mitogen-activated protein kinases (MAPKs)-associated pathways involved in cellular proliferation.…”

Beneficial effect of heat-killed Lactiplantibacillus plantarum L-137 on intestinal barrier function of rat small intestinal epithelial cells

“…On the other hand, TJ proteins are known to be involved in the regulation of the leak pathway 59 , 60 . ZO-1, a TJ scaffold protein, is considered a regulator of the leak pathway, and ZO-1 depletion was reported to disrupt the leak pathway 9 , 57 . ZO-1 interacts with the transmembrane proteins claudin and occludin, with cytoskeletal F-actin, and with myosin and other signaling proteins and is essential for TJ and cytoskeletal structure; however, its role is not clearly understood 9 .…”

“…ZO-1, a TJ scaffold protein, is considered a regulator of the leak pathway, and ZO-1 depletion was reported to disrupt the leak pathway 9 , 57 . ZO-1 interacts with the transmembrane proteins claudin and occludin, with cytoskeletal F-actin, and with myosin and other signaling proteins and is essential for TJ and cytoskeletal structure; however, its role is not clearly understood 9 . On the other hand, paracellular permeability was reported to be reduced by upregulation of endogenous ZO-1 expression 61 .…”

“…TJ formation involves several proteins, including the transmembrane proteins occludin and claudin-1 and zonula occludens-1 (ZO-1), a cytoplasmic protein that binds to these transmembrane proteins 8 . Studies have reported that promoting TJ function improves intestinal barrier function and may be effective in preventing and treating leaky gut 9 , 10 .…”